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D Del Principe

Publications and source records attributed to D Del Principe.

At least 19 recordsLinked to original sources
PubMed2003

[Antithrombin III in burned children].

We studied haemostatic parameter and Antithrombin III (ATIII) level in 50 consecutive admissions for severe burns between 1990 to1994 to the Centro Grandi Ustionati Ospedale S. Eugenio, Rome. The criteria for inclusion in the study were age <16 years and the presence of major burns (extent of the burns >30 and second and third degree burns). Treatment consisted of initial fluid resuscitation and early excision and grafting of burn wounds and critical care support by a multidisciplinary team. Burn-related variables haemostatic values and the conditions of microcirculation were proposed and analysed with the help of Fisher exact test, chi square test, logistic regression and discriminant analysis. By the discriminant analysis, the coefficients of the standardized functions and the percentage of correctly classified individuals were calculated. The analysis showed total burned surface turned out to be the best predictor of survival. High discrimination efficiency was observed for age, weight, burn type (flame, scald contact chemical electrical). By the logistic regression, the total burned surface confirmed to be the best predictor of survival and between the haemostatic variables ATIII give a significant value (p=0.0244). Moreover, it is noteworthy that ATIII level at the onset of the disease gives a significant correlation with mortality (p=0.0005). The Fisher test showed a significant association between ATIII level and death (p=0.0005). This was confirmed by the chi square test (p=0.00027). Considering the AT deficiency in patients with thermal injuries, we conducted a pilot study to assess AT concentrate infusions for safety and efficacy in thermal injury. The patients received AT concentrate infusions every 8 hours to raise the plasma level to 100 % in the first 72 hours after injury and were compared with control patients with burns. Day4 levels were 105%+/-20% in patients treated with AT patients versus 50%+/-14% in the control patients (P < 0.001). In the group treated with AT the time to microcirculation recovery was shorter (P<0.02).

Adolescent↗
PubMed2001

Involvement of oxygen radicals in cytarabine-induced apoptosis in human polymorphonuclear cells.

We investigated apoptosis in polymorphonuclear neutrophils (PMNs) induced by cytarabine (Ara-C). This drug increased apoptosis by 100% with respect to the controls after 3 hr of incubation. This increase was inhibited by N-acetyl-L-cysteine (NAC) or diphenyleneiodonium chloride (DPI). Ara-C alone caused an early increase (after a 30-min incubation) in intracellular oxidant generation (inhibitable by rotenone, fumonisin b1, and DPI) and in protein tyrosine phosphorylations (inhibitable by NAC). The drug also affected the observed reduction of dimethylthiazol diphenyltetrazolium bromide (MTT). No extracellular release of reactive oxygen species (ROS) was elicited by the addition of Ara-C, while the drug increased the release of ROS by N-formyl-leucyl-phenylalanine-(f-MLP) but not phorbol 12-myristate 13-acetate-stimulated PMNs. This phenomenon was abolished by the addition of genistein, whereas such an effect was not observed following the addition of 1-(5-isoquinolynilsulfonyl)-2-methylpiperazine (H7). Ara-C induced ROS release from PMNs in the presence of subthreshold concentrations of f-MLP (priming effect). These results indicate that intracellular ROS production from mitochondria promotes Ara-C-induced apoptosis. Ara-C primes plasma membranes by a mechanism involving protein tyrosine phosphorylations and may also contribute to ROS generation from the granules.

Antimetabolites, Antineoplastic↗
PubMed2001

Human platelets bind and degrade 2-arachidonoylglycerol, which activates these cells through a cannabinoid receptor.

The endocannabinoid 2-arachidonoylglycerol (2-Delta(4)Ach-Gro) activates human platelets in platelet-rich plasma at physiological concentrations. The activation was inhibited by selective antagonists of CB(1) and CB(2) cannabinoid receptors, but not by acetylsalicylic acid. Human platelets can metabolize 2-Delta(4)Ach-Gro by internalization through a high affinity transporter (K(m) = 300 +/- 30 nM, V(max) = 10 +/- 1 pmol.min(-1).mg protein(-1)), followed by hydrolysis by a fatty acid amide hydrolase (K(m) = 8 +/- 1 microM, V(max) = 400 +/- 50 pmol.min(-1).mg protein(-1)). The anandamide transport inhibitor AM404, and anandamide itself, were ineffective on 2-Delta(4)Ach-Gro uptake by platelets, whereas anandamide competitively inhibited 2-Delta(4)Ach-Gro hydrolysis (inhibition constant = 10 +/- 1 microM). Platelet activation by 2-Delta(4)Ach-Gro was paralleled by an increase of intracellular calcium and inositol-1,4,5-trisphosphate, and by a decrease of cyclic AMP. Moreover, treatment of preloaded platelet-rich plasma with 2-Delta(4)Ach-Gro induced an approximately threefold increase in [(3)H]2-Delta(4)Ach-Gro release, according to a CB receptor-dependent mechanism. On the other hand, ADP and collagen counteracted the activation of platelets by 2-Delta(4)Ach-Gro, whereas 5-hydroxytryptamine (serotonin) enhanced and extended its effects. Remarkably, ADP and collagen also reduced [(3)H]2-Delta(4)Ach-Gro release from 2-Delta(4)Ach-Gro-activated platelets, whereas 5-hydroxytryptamine further increased it. These findings suggest a so far unnoticed interplay between the peripheral endocannabinoid system and physiological platelet agonists.

Adenosine Diphosphate↗
PubMed2000

Spectrin changes occur in erythrocytes from patients with Fanconi's anemia and their parents.

Fanconi's anemia (FA) is a clinically and genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. In this work we report the results obtained by morphometric analyses on the red blood cells (RBCs) from FA patients and their parents. We found that a high rate of erythrocytes from both homozygous and heterozygous subjects was significantly altered. RBCs underwent in fact cytoskeleton-dependent modifications, in particular of spectrin molecule, leading to cell shrinking and blebbing. We hypothesize that these changes may be the result of an oxidative imbalance that probably lead to alterations of RBC plasticity- and deformation-associated functions. Moreover, our results also suggest the possibility to identify FA carriers by the existence of RBC abnormalities.

Adolescent↗
PubMed2000

Cytoskeleton alterations of erythrocytes from patients with Fanconi's anemia.

Fanconi's anemia (FA) is a very rare genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. In this work we report the results obtained by morphometric and biochemical analyses on the red blood cells (RBCs) from FA patients. With respect to RBCs from healthy donors the following changes have been detected: (i) a variety of ultrastructural alterations, mainly surface blebbing typical of acanthocytes and stomatocytes; (ii) a significant quantitative increase of these altered forms; (iii) modifications of spectrin cytoskeleton network; (iv) an altered redox balance, e.g. a decreased catalase activity and significant variations in the GSSG/GSH ratio. We hypothesize that remodeling of the redox state occurring in FA patients results in cytoskeleton-associated alterations of red blood cell integrity and function.

Adolescent↗
PubMed2000

Surface reactions of a plasma-sprayed CaO-P2O5-SiO2-based glass with albumin, fibroblasts and granulocytes studied by XPS, fluorescence and chemiluminescence.

X-ray photoelectron spectroscopy (XPS) was used to define the chemical composition of the outermost surface layer and the surface modification of a plasma-coated phospho-silicate glass (identified as BVA) when immersed in K-phosphate buffer or in phosphate buffered human albumin solution. Its behavior was compared with that of a soda-lime-based glass (identified as BVH) treated in the same way. The surface % composition of plasma-sprayed glass was consistent with bulk composition. After incubation with buffer, a Ca-P-rich layer developed only on the surface of BVA glass. Human serum albumin was bound reversibly to both glasses maintaining its native state. However, the protein completely covered the BVA glass surface within 24 h, with the formation of a mixed albumin-Ca-P layer, while 4 days incubation was necessary for complete coverage of BVH glass surface. Murine fibroblasts seeded on plasma-coated BVA glass showed a proliferation pattern similar to that of control cells grown on Petri dish, while cells seeded on BVH had more restricted growth. A limited response was induced in polymorphonuclear granulocytes by both bulk glasses powder. In conclusion, the glass identified as BVA has the suitable characteristics of its surface layers to be considered biologically active from both a chemical and a cellular point of view.

3T3 Cells↗
PubMed2000

Acute childhood idiopathic thrombocytopenic purpura: AIEOP consensus guidelines for diagnosis and treatment. Associazione Italiana di Ematologia e Oncologia Pediatrica.

BACKGROUND AND OBJECTIVE: A recent evaluation carried out by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) about practice management of acute childhood idiopathic thrombocytopenic purpura (ITP) revealed a remarkable difference of behaviors among the different AIEOP centers. A need for common practice guidelines for this frequent illness arose from this observation. Our aim was to make the diagnosis and treatment of childhood ITP uniform. In the future we will evaluate the influence of these guidelines on practice behaviors. DATA SOURCES AND METHODS: Our main reference was the 1996 document produced by the American Society of Hematology (ASH). Their recommendations were updated with information from literature searched for in the MEDLINE database (June 1996-October 1998); search terms included: thrombocytopenia, ITP, diagnosis, therapy, children. The computerized search retrieved 83 articles. DATA EXTRACTION: the scientific validity of the literature was evaluated by a panel of members using published guidelines. The strength of the evidence was assessed using level of evidence criteria. Only data from level I and level II studies were taken in account. Only one study out of the 83 retrieved articles met these selection criteria and it was considered in addition to the 11 out of 581 articles selected in the ASH ITP guidelines. This preliminary work pointed out each issue about ITP not addressed by clinical studies and all participants in a Consensus Conference expressed their opinion about these issues. RESULTS: Diagnosis is essentially based on history, physical examination, a complete blood count and an examination of the peripheral blood smear. Treatment is recommended taking into account the clinical picture and number of platelets. The main difference between these guidelines and those from ASH are: AIEOP guidelines rely on the opinion of the members of the consensus conference, ASH ones on a panel of experts; therapeutic options include only products available in Italy; the indications to treatment rely more on clinical picture than on platelet number. INTERPRETATION AND CONCLUSIONS: These are explicitly developed, evidence-based practice guidelines to assist Italian pediatricians in making decisions about diagnosis and appropriate health care for patients with acute childhood ITP.

Acute Disease↗
PubMed1999

Anandamide activates human platelets through a pathway independent of the arachidonate cascade.

Anandamide (arachidonoylethanolamide, AnNH) is shown to activate human platelets, a process which was not inhibited by acetylsalicylic acid (aspirin). Unlike AnNH, hydroperoxides generated thereof by lipoxygenase activity, and the congener (13-hydroxy)linoleoylethanolamide, were unable to activate platelets, though they counteracted AnNH-mediated stimulation. On the other hand, palmitoylethanolamide neither activated human platelets nor blocked the AnNH effects. AnNH inactivation by human platelets was afforded by a high-affinity transporter, which was activated by nitric oxide-donors up to 225% of the control. The internalized AnNH could thus be hydrolyzed by a fatty acid amide hydrolase (FAAH), characterized here for the first time.

Adenosine Diphosphate↗
PubMed1999

Effect of amlodipine on exercise-induced platelet activation in patients affected by chronic stable angina.

BACKGROUND: Literature concerning exercise-induced platelet activation in chronic stable angina is somewhat confusing. The reason lies in the type of exercise as well as in methodological problems. A powerful, recently introduced procedure to detect platelet activation is flow cytometry. Platelet response to activating factors is mediated by calcium uptake; however, calcium antagonist effect on platelet activity is still unclear. HYPOTHESIS: The study was undertaken to investigate exercise-induced platelet activation before and after treatment with amlodipine in chronic stable angina. METHODS: Twenty patients with chronic stable angina were entered into the study. Each subject underwent a symptom-limited cycloergometer stress test following a washout period of 2 weeks. Blood samples were collected before and immediately after exercise. All subjects were then randomized into two groups of 10 patients each, with Group 1 and Group 2 taking amlodipine 10 mg/day, and placebo for 4 weeks, respectively. They subsequently underwent a second exercise stress test, and blood samples were obtained before and immediately after exercise. Flow-cytometric evaluation of platelet activity was performed in order to recognize GMP-140 expression on platelet membrane. RESULTS: Strenuous exercise induced a significant increase in platelet activation in all subjects prior to therapy. No significant differences were observed in platelet activity at rest between Groups 1 and 2, whereas a significant decrease in exercise-induced platelet activation was demonstrated in Group 1 compared with Group 2. CONCLUSION: Our data provide evidence of the favorable effect of amlodipine on exercise-induced platelet activation in patients affected by chronic stable angina.

Aged↗
PubMed1998

Livedo vasculopathy vs small vessel cutaneous vasculitis: cytokine and platelet P-selectin studies.

OBJECTIVE: To assess the role of platelets and lymphocyte-related immunological mechanisms in livedo vasculopathy (LV) and cutaneous small vessel vasculitis (CSVV). Livedo vasculopathy is thought to be related to the thrombotic occlusion of small and medium-sized dermal vessels. Cutaneous small vessel vasculitis comprises a heterogeneous group of disorders in which the main pathogenetic events could be modulated by circulating cytokines. DESIGN: Case series study of 2 groups of patients affected respectively with LV and CSVV. SETTING: A large clinical and research institute for the study and treatment of cutaneous diseases. PATIENTS: Consecutive patients with clinically and histologically proved idiopathic LV (n = 8) and CSVV (n = 20) were studied and compared with healthy donors (n = 20). Patients with potentially correlated systemic diseases were excluded. MAIN OUTCOME MEASURES: Surface expression of platelet P-selectin and circulating level of interleukin (IL) 1beta, tumor necrosis factor alpha (TNF-alpha), IL-8, IL-2, and soluble IL-2 receptor. RESULTS: The IL-2 and soluble IL-2 receptor levels were significantly higher in serum samples from patients with both LV (1.24 +/- 0.46 IU/mL [mean +/- SD] vs 0.46 +/- 0.24 IU/mL, P<.001; 899 +/- 368 IU/mL vs 628 +/- 132 IU/mL, P<.02) and CSVV (0.91 +/- 0.57 IU/mL, P<.02; 1087 +/- 451 IU/mL, P<.001) than in those from the healthy controls. The serum levels of IL-1beta, TNF-alpha, and IL-8 were higher in patients with CSVV than in controls (7.53 +/- 6.7 pg/mL vs 4.58 +/- 2.72 pg/mL; 23.7 +/- 12.6 pg/mL vs 10.82 +/- 2.46 pg/mL, P<.001; 37.8 +/- 46 pg/mL vs 8.25 +/- 3.53 pg/mL, P<.02, respectively). No significant difference in the serum levels of IL-1beta (7.2 +/- 4.9 pg/mL), TNF-alpha (12.9 +/- 3.47 pg/mL), and IL-8 (5.9 +/- 4.13 pg/mL) was observed in patients with LV compared with controls. An increased expression of platelet P-selectin was also detected in patients with LV in comparison with controls and patients with CSVV. The mean +/- SD percentage of positive cells for P-selectin was 43% +/- 5% in the patients with LV, 5.1% +/- 2% in the controls (P<.001), and 5.3% +/- 2% in the patients with CSVV (P<.001). CONCLUSIONS: Taken together, these data demonstrate that different pathogenetic mechanisms are operative in LV and CSVV. In fact, platelet and lymphocyte activation is present in LV, whereas the levels of inflammatory mediators are in a normal range. In CSVV, the high serum levels of proinflammatory cytokines suggest that they are actively involved in the pathogenesis of cutaneous vasculitis.

Adult↗
PubMed1997

Fibroblast growth and polymorphonuclear granulocyte activation in the presence of a new biologically active sol-gel glass.

The search for chemical devices to be used in clinical orthopaedics must find substances that are biocompatible and do not elicit inflammatory responses in vivo. To this end, a new form of glass has been prepared, composed of 8.1% CaO, 2.9% P2O5, 6.7% N2O5 and 82.3% SiO2, using sol-gel procedures. In order to evaluate the in vitro biocompatibility of this glass, the proliferation of cultured murine fibroblasts and the activation of human polymorphonuclear leukocytes has been studied. The performance of the sol-gel glass has been compared with that of a biocompatible non-resorbable soda-lime glass. Unlike the soda-lime glass, the sol-gel glass neither caused the inhibition of fibroblast growth nor elicited a marked inflammatory response by polymorphonuclear leukocytes, as demonstrated by chemiluminescence assay for reactive oxygen metabolites.

Journal Article↗
PubMed1996

Fanconi anaemia in Italy: high prevalence of complementation group A in two geographic clusters.

Cell fusion studies using lymphoblastoid cell lines from Fanconi anaemia (FA) patients have identified five complementation groups (FA-A to FA-E) among European FA patients. In Italy, of the 45 FA families referred to the Italian Registry of Fanconi Anaemia (RIAF), 15 took part in a project for the identification of complementation groups. Since three immortalized lymphoblast lines were resistant to a cross-linking agent, we analysed only 12 patients by complementation analysis and found that 11 belong to complementation group A. Four and seven families came from two geographic clusters in the Veneto and Campania regions, respectively, which are thought to consist of aggregates of related families in reproductive isolation. The clinical characteristics of the patients showed both intra- and interfamilial heterogeneity, although overall the disease had a relatively mild course. Since the populations in both Veneto and Campania are likely to represent genetic isolates, our finding predicts linkage disequilibrium for markers flanking the FAA gene. DNAs from these FA families may thus be utilized for positional cloning of this gene through haplotype disequilibrium mapping.

Cell Fusion↗
PubMed1995

Effect of insulin on hydrogen peroxide production by human polymorphonuclear leukocytes. Studies with monoclonal anti-insulin receptor antibodies, and an agonist and an inhibitor of protein kinase C.

This study evaluated the effect of insulin on the respiratory burst of human polymorphonuclear leukocytes (PMNLs) and the signalling pathways involved in this process, especially the involvement of protein kinase C (PKC). Isolated human PMNLs from healthy volunteers were incubated with different concentrations of insulin (10-10-10-7 mol/l) and for different durations of incubation (5-90 min). The intracellular production of hydrogen peroxide (H2O2) was detected employing a previously validated flow cytometric assay using 2',7'-dichlorofluorescein-diacetate (DCFH-DA) as a marker for H202 production. Specificity of insulin action was verified using an insulin antagonist (the monoclonal antibody MA-10). To identify the signalling pathway involved, we used; (a) monoclonal antibody MA-5, directed against the alpha-subunit of the insulin receptor, that partially mimics insulin without activating tyrosine kinase; (b) H7, an inhibitor of PKC involved in O2- production in PMNLs, and (c) phorbol myristate acetate (PMA) that binds and stimulates PKC. Insulin caused a dose- and time-dependent stimulation of H202 release by human PMNLs. The effect of insulin was blocked MA-10. The actions of insulin and PMA on H2O2 release were additive, whereas the actions of MA-5 and PMA were not. H7 partially inhibited the H2O2 production stimulated by insulin and completely inhibited MA-5 action. We conclude that insulin stimulates, in a dose- and time-related manner, the respiratory burst of human PMNLs. PKC activation can only partially account for the intracellular mechanisms involved in this process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Detection by capillary electrophoresis of restriction fragment length polymorphism. Analysis of a polymerase chain reaction-amplified product of the DXS 164 locus in the dystrophin gene.

Capillary electrophoresis (CE) was used to characterize restriction fragment length polymorphism (RFLP) in a polymerase chain reaction (PCR)-amplified product of a 740-base pairs DNA fragment from the DXS 164 locus of the dystrophin gene. The polymorphic alleles of 740 and 520/220 base pairs revealed by XmnI digestion were analysed from homozygous and heterozygous individuals by CE. Our studies show that extraction in phenol-chloroform may be useful in PCR-amplified product purification. Excellent separation was obtained in a short time. The data indicate that CE is suitable for genomic analysis such as carrier detection and prenatal diagnosis of X-linked recessive disorders after purification of PCR-amplified products.

Adult↗
PubMed1993

PADGEM/GMP-140 expression on platelet membranes from homozygous beta thalassaemic patients.

Thromboembolic events, which are associated with significant morbidity and mortality, occur in beta-thalassaemia. We studied the expression of the platelet selectin PADGEM/GMP-140 on intact cells from thalassaemic patients, as a marker of in vivo platelet activation. The mean of positive cells (%) was 38.143 +/- 20.65 in the patients versus 5.048 +/- 1.8 in the controls, n = 21, P < 0.001. No correlation was found between GMP-140 expression and splenectomy, platelet counts, plasma ferritin and natural coagulation inhibitors. Instead an indirect correlation was found between GMP-140 expression and HDL-cholesterol. Moreover platelet activation was directly correlated with pre-beta lipoproteins. Our data indicate that thalassaemic patients present an in vivo platelet activation, which possibly depends on the dyslipidaemia, which is now regarded as a frequent feature of this disease.

Adolescent↗